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Pathogenesis and Immunity

Efficient Processing of the Immunodominant, HLA-A*0201-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitope despite Multiple Variations in the Epitope Flanking Sequences

Christian Brander, Otto O. Yang, Norman G. Jones, Yun Lee, Philip Goulder, R. Paul Johnson, Alicja Trocha, David Colbert, Christine Hay, Susan Buchbinder, Cornelia C. Bergmann, Hans J. Zweerink, Steven Wolinsky, William A. Blattner, Spyros A. Kalams, Bruce D. Walker
Christian Brander
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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Otto O. Yang
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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Norman G. Jones
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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Yun Lee
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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Philip Goulder
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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R. Paul Johnson
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
New England Regional Primate Center, Harvard Medical School, Southborough, Massachusetts 01772;
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Alicja Trocha
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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David Colbert
HIV Research Section, Department of Public Health, San Francisco, California 94102;
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Christine Hay
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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Susan Buchbinder
HIV Research Section, Department of Public Health, San Francisco, California 94102;
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Cornelia C. Bergmann
University of Southern California School of Medicine, Los Angeles, California 90033;
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Hans J. Zweerink
Department of Inflammation and Rheumatology, Merck Research Laboratories, Rahway, New Jersey 07065;
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Steven Wolinsky
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611; and
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William A. Blattner
Division of Geographic Medicine, University of Maryland, Baltimore, Maryland 21201
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Spyros A. Kalams
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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Bruce D. Walker
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;
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DOI: 10.1128/JVI.73.12.10191-10198.1999
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ABSTRACT

Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immunogenic peptide. However, the frequency of such an escape mechanism has not been determined. To investigate whether naturally occurring variations in the flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag sequences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants were efficiently processed from minigene expressing vectors and from six HIV-1 Gag variants expressed by recombinant vaccinia virus constructs. Furthermore, SL9-specific CTL clones derived from multiple donors efficiently inhibited virus replication when added to HLA-A*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immunodominant CTL response is not frequently accomplished by changes in the epitope flanking sequences.

  • Copyright © 1999 American Society for Microbiology
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Efficient Processing of the Immunodominant, HLA-A*0201-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitope despite Multiple Variations in the Epitope Flanking Sequences
Christian Brander, Otto O. Yang, Norman G. Jones, Yun Lee, Philip Goulder, R. Paul Johnson, Alicja Trocha, David Colbert, Christine Hay, Susan Buchbinder, Cornelia C. Bergmann, Hans J. Zweerink, Steven Wolinsky, William A. Blattner, Spyros A. Kalams, Bruce D. Walker
Journal of Virology Dec 1999, 73 (12) 10191-10198; DOI: 10.1128/JVI.73.12.10191-10198.1999

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Efficient Processing of the Immunodominant, HLA-A*0201-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitope despite Multiple Variations in the Epitope Flanking Sequences
Christian Brander, Otto O. Yang, Norman G. Jones, Yun Lee, Philip Goulder, R. Paul Johnson, Alicja Trocha, David Colbert, Christine Hay, Susan Buchbinder, Cornelia C. Bergmann, Hans J. Zweerink, Steven Wolinsky, William A. Blattner, Spyros A. Kalams, Bruce D. Walker
Journal of Virology Dec 1999, 73 (12) 10191-10198; DOI: 10.1128/JVI.73.12.10191-10198.1999
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KEYWORDS

antigen presentation
Epitopes, T-Lymphocyte
Gene Products, gag
HIV Antigens
HIV Infections
HIV-1
HLA-A2 Antigen
Immunodominant Epitopes
T-Lymphocytes, Cytotoxic
Viral Proteins

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